Rob Ramsay has had a long standing research commitment to understanding bowel and breast cancer using mouse models with defined genetic defects. These sophisticated models replicate various stages of cancer development and some have profound effects on normal tissue biology. He also uses molecular tools to investigate how genes are controlled. These approaches are providing direct input into the development of therapeutic agents for cancer treatment.
DOES BCL-G, A BH3-ONLY PROTEIN, PLAY A ROLE IN INFLAMMATION-ASSOCIATED COLON CANCER?
Funder
National Health and Medical Research Council
Funding Amount
$418,587.00
Summary
Deregulation of the function of several members of the Bcl-2 family has been shown to be an aggravating factor in autoimmune diseases and cancer. Bcl-G is a new and poorly characterized member of this family. We have produced essential tools to study the physiological function of Bcl-G, and discovered that it plays a role in inflammatory bowel disease. We now plan to investigate its possible role in inflammation-associated colon cancer.?
Potential Roles Of 5-hydroxytryptamine In Diseases Affecting The Colon
Funder
National Health and Medical Research Council
Funding Amount
$346,018.00
Summary
The overall aim of this project is to examine the biological roles played by 5-hydroxytryptamine (5-HT) in the human colon. 5-HT is a naturally occurring substance of the body, normally involved in controlling many body activities. Relevance is placed in this project on the possibility that 5-HT is involved in causing or contributing to certain clinical conditions, either by excess or deficiency. The conditions that are the focus of this project are chronic constipation, diverticular disease and ....The overall aim of this project is to examine the biological roles played by 5-hydroxytryptamine (5-HT) in the human colon. 5-HT is a naturally occurring substance of the body, normally involved in controlling many body activities. Relevance is placed in this project on the possibility that 5-HT is involved in causing or contributing to certain clinical conditions, either by excess or deficiency. The conditions that are the focus of this project are chronic constipation, diverticular disease and irritable bowel syndrome. It is a matter of concern that there are no specific treatments for these conditions to date, hence the thrust of the project is to increase knowledge in this area, so hopefully treatments will be developed. Our Pharmacology research group is recognised for its experience in defining drug effects on the intestine and in characterising the target sites on which they act. This has been achieved by using an integrated approach whereby different functional methods reliably detect effects at the levels of the muscle layers, the nerves that supply them and at the absorptive surface using experimental animals. In addition, the use of isolated pieces of human colon obtained from discarded operation material has been an invaluable inclusion into this process. This has allowed us to establish that 5-HT has a target site in the muscle of the colon and that this leads to relaxation and inhibition of the normal spontaneous contractile activity, said anecdotally to be abnormally high in patients with irritable bowel syndrome. We now wish to apply this expertise and knowledge to test whether 5-HT is involved in causing chronic constipation and diverticular disease and to design a drug that would be expected to be of value in treating patients with irritable bowel syndrome.Read moreRead less
Investigation Of DUSP5 As A Novel Tumour Suppressor Gene In Colon Cancer
Funder
National Health and Medical Research Council
Funding Amount
$578,268.00
Summary
Colon cancer is the second leading cause of cancer related death in Australia. Understanding the genetic causes of this disease are essential to developing new treatment strategies. The goal of this study is to understand the role of the DUSP5 gene in colon cancer. The findings of this study has the potential to further our understanding of how colon cancers arise and for identifying patients likely to respond to specific existing treatments.
Role Of The EHF Transcription Factor In Regulating The Differentiation Status Of Colon Cancers
Funder
National Health and Medical Research Council
Funding Amount
$621,950.00
Summary
New treatment strategies for colon cancer are urgently needed. This application will test a novel approach for treating colon cancer based on the re-induction of differentiation of colon cancer cells, by reactivating a gene called EHF. We expect this to reduce the propensity for colon cancer cells to spread to distant organs and to increase their sensitivity to chemotherpay. This has the potential to significantly benefit the clinical management of patients with this disease.
Hemokinin - A New Inflammatory Mediator In The Intestine.
Funder
National Health and Medical Research Council
Funding Amount
$382,768.00
Summary
Inflammatory bowel disease and acute diverticular disease are two serious and very costly inflammatory disorders of the bowel. Tachykinins are known to be causally involved in inflammation-induced bowel dysfunction. A new tachykinin peptide, hemokinin, is found in immune cells, but has not been studied at all in the intestine. In this project, we will study the effects of hemokinin on human bowel immune function. The study will provide essential information to formulate new treatments.
I am a molecular-cell biologist studying the genetic regulation of intestinal homeostasis in development and disease with the aim of identifying novel molecular targets for the treatment of disease and that can be validated in relevant preclinical mouse models.
This project aims to develop a new therapy for colorectal cancer (CRC). We have already demonstrated that a molecule called PAK1 is the master regulator of several intracellular signalling pathways, and is essential for CRC growth and invasion. We now plan to study whether inhibitors that block PAK1 activity can prevent the growth of human CRC cells in the laboratory or their development into tumours in animals.